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Ghrelin May Play Role in Alcohol Dependence

Last Updated: July 02, 2009.

In addition to its already known function in the regulation of eating, central ghrelin signaling appears to be necessary for the rewarding properties of alcohol, according to research published online June 29 in Proceedings of the National Academy of Sciences.

THURSDAY, July 2 (HealthDay News) -- In addition to its already known function in the regulation of eating, central ghrelin signaling appears to be necessary for the rewarding properties of alcohol, according to research published online June 29 in Proceedings of the National Academy of Sciences.

Elisabet Jerlhag, Ph.D., of the University of Gothenburg in Sweden, and colleagues discuss several experiments using mice. The authors found that administering ghrelin into the third ventricle and into the ventral tegmental area or laterodorsal tegmental area -- structures involved in reward -- increased mice's consumption of alcohol. However, administering ghrelin receptor (GHS-R1A) antagonists, peripherally or centrally, reduced their alcohol intake.

In addition, the researchers found, GHS-R1A knockout mice and animals treated with two GHS-R1A antagonists showed decreased alcohol-induced locomotor stimulation and alcohol-induced enhanced extracellular accumbal dopamine release. Both of these are thought to play a role in the addiction process and are associated with alcohol reinforcement.

"The finding that alcohol intake can be suppressed by administration of a GHS-R1A antagonist implies that orally bioavailable, brain penetrant GHS-R1A antagonists may have therapeutic potential in alcohol use disorders. Our studies also raise important questions regarding the physiological role of ghrelin, a gut-brain signal, influencing not only hunger but clearly also having a broader role in the search for rewarding substances such as alcohol," the authors conclude.

The research was supported in part by Novo Nordisk and a Swedish alcohol retail group.

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